One of the main functions of the normal, healthy kidney, besides its regulatory, endocrine, and metabolic functions, is the disposal of waste products. Any impairment of excretory function can lead to the accumulation of a variety of nitrogenous waste products including, urea, creatinine and uric acid. High concentrations of waste products in the blood stream can exacerbate renal failure and promote kidney stones. Moreover, nitrogenous solutes in the circulating blood promote osmotic diffusion into the lumen because of the concentration gradient across the intestinal wall. This diffusion mechanism led to the concept of oral sorbents to augment gut-based clearance of nitrogenous waste products. Sorbents or microbes have demonstrated their ability to remove various compounds and nitrogenous wastes within the large bowel.
Urea-specific sorbents such as synthetic polymers and modified polysaccharides have been evaluated for the removal of urea and other nitrogenous wastes via the gut. Other sorbents such as oxidized starch, activated charcoal, and carob flour have also been investigated for the in vivo elimination of uremic toxins with some success. Prakash & Chang ((1996) Nature Medicine 2:883-88) demonstrated that microencapsulated, genetically-engineered E. coli DH5 are effective in removing urea and ammonia in an in vitro system. The same researchers obtained similar results in oral administration of E. coli DH5 cells in a uremic rat animal model. Bliss et al. ((1996) Am. J. Clin. Nutr. 63:392-398) have demonstrated that supplemental gum arabic fiber increases fecal nitrogen excretion and lowers urea nitrogen concentration in chronic renal failure patients consuming a low protein diet. Reinhart et al. ((1998) Rec. Adv. In Canine and Feline Nutr. Iams Nutrition Symposium Proceedings. Vol. II:395-404) found that canine renal patients fed a diet containing a fermentable fiber blend improved clinical end-stage renal disease status, suggesting that specific nutritional alteration allows repartitioning of nitrogen excretion away from the kidney and into the feces by colonic fermentation or additional bacterial growth.
Prebiotic components are food ingredients that enhance the actions of probiotic components in the digestive tract. In this synergistic or synbiotic relationship a probiotic component, such as Bifidobacteria, metabolizes undigested carbohydrates, such as dietary fibers, oligosaccharides, etc., to produce short-chain fatty acids such as acetate, propionate and butyrate. These short-chain fatty acids may promote intestinal cell growth, enhance water and mineral absorption, and prevent yeast, mold, and pathogenic bacterial growth. In addition, probiotic components may antagonize pathogens directly through production of antimicrobial and antibacterial compounds such as cytokines and butyric acid (De Vuyst and Vandamme. Antimicrobial potential of lactic acid bacteria. In: De Vuyst L, Vandamme E L, eds. Bacteriocins of lactic acid bacteria. Glasgow, United Kingdom: Blackie Academic and Professional; 1994:91-142; Dodd and Gasson. Bacteriocins of lactic acid bacteria. In: Gasson M J, de Vos W M, eds. Genetics and biotechnology of lactic acid bacteria. Glasgow, United Kingdom: Blackie Academic and Professional; 1994:211-51; Kailasapathy and Chin (2000) Immunol. Cell. Biol. 78(1):80-8), reduce gut pH by stimulating the lactic acid-producing microflora (Langhendries et al. (1995) J. Pediatr. Gastroenterol. Nutr. 21:177-81), compete for binding and receptor sites that pathogens occupy (Kailasapathy and Chin (2000) Immunol. Cell. Biol. 78(1):80-8; Fujiwara et al., (1997) Appl. Environ. Microbiol. 63:506-12), improve immune function and stimulate immunomodulatory cells (Isolauri et al. (1991) Pediatrics 88:90-97; Isolauri et al. (1995) Vaccine 13:310-312; Rolfe (2000) J. Nufr. 130(2S):396S-402S), compete with pathogens for available nutrients and other growth factors (Rolfe (2000) J. Nufr. 130(2S):396S-402S), or produce lactase which aids in lactose digestion.
U.S. Pat. No. 4,022,883 discloses a method for alleviating uremic symptoms in persons suffering from renal failure comprising administering orally thereto an effective dosage of a cell mass of a non-pathogenic soil bacteria selected from the group consisting of an urea degrading bacterium, a creatine degrading bacterium, a creatinine degrading bacterium and an uric acid degrading bacterium wherein the urea degrading bacterium is a species of Serratia; the creatinine degrading bacterium is a non-fluorescent Pseudomonas, Rhizobium, Agrobacterium, Corynebacterium ureafaciens, Arthrobacter ureafaciens, E. coli, or Pseudomonas aeruginosa; and a uric acid degrading bacterium is Bacillus subtilis, a non-fluorescent Pseudomonas, Bacillus fastidosus, Micrococcus dentrificans, Mycobacterium phlei, Aerobacter aerogenes. 
U.S. Pat. No. 4,218,541 teaches a method for converting urea to innocuous products. The method involves obtaining a culture of at least one microorganism selected from the group of Enterobacter agglomerans, Group D Streptococcus, Bacilli, and Pseudomonad or mixtures of said microorganisms and adding the culture to a composition containing urea.
U.S. Pat. No. 4,970,153 discloses a method of producing urease and more particularly a method of producing acid urease by the cultivation of Lactobacillus fermentum TK 1214. This patent further teaches the use of such acid urease or the decomposition of urea contained in fermentation food products.
U.S. Pat. No. 5,116,737 teaches a method for growing acid-producing bacterial cultures, such as diary cultures, wherein the culture is selected to contain a urease-producing strain of bacteria and the medium used for the culturing contains added urea. Urease-producing strains of Streptococcus thermophilus and Bifidobacterium are also disclosed.
U.S. Pat. No. 5,716,615 discloses a pharmaceutical composition containing several different bacteria including Streptococcus thermophilus, Lactobacilli and Bifidobacteria wherein the bacteria are present in the composition at a total concentration of 1×1011 to 1×1013 per gram. An excipient consisting of maltodextrin, microcrystalline cellulose, maize starch, levulose, lactose or dextrose is further taught. Methods of using the pharmaceutical composition are also disclosed which include treatment of a gastrointestinal disorder and hypercholesteremia or modulating a host's immune response.
The present invention combines the beneficial effects of prebiotic and probiotic components into a synbiotic product that effectively reduces nitrogenous wastes.